ABSTRACT The incidence of neonatal opioid withdrawal syndrome (NOWS) increased greater than 5-fold between 2004 to 2014. Despite the significance of this problem, numerous critical gaps remain with respect to the best practices for identification and management of infants with NOWS, along with our understanding of the outcomes of these infants. Variation in pediatric medical care is common and contributes to differences in patient outcomes. The IDeA States Pediatric Clinical Trials Network (ISPCTN), which is part of the Environmental influences on Child Health Outcomes (ECHO) Program, and the Neonatal Research Network (NRN) are uniquely poised to address existing knowledge gaps associated with NOWS. The ISPCTN consists of >20 neonatal intensive care units and the NRN consists of >50 neonatal intensive care units. We are leveraging the ISPCTN and the NRN to complete two clinical trials to evaluate interventions to improve the care of infants and families affected by NOWS: 1) a clinical trial protocol evaluating the optimal use of the Eating, Sleeping, Consoling (ESC) care approach on the length of time until infants affected by NOWS are medically ready for discharge (24 site, >1000 infants); and 2) a clinical trial protocol evaluating whether an early stop weaning protocol for morphine in infants treated for NOWS will decrease the number of days of opioid treatment (25 sites, 500 infants). The goal of this project is to develop data standards for use in clinical research within the infants with in utero opioid exposure community. We will provide common data elements (CDEs) and reporting formats to assist researchers quantify the severity of withdrawal among infants with NOWS using the Finnegan Neonatal Abstinence Scoring Tool (FNAST) or the ESC from the ESC Trial. We will develop harmonized severity of withdrawal among infants with NOWS definitions for clinical research and patient registries by using existing data elements and creating new data elements, when needed.